Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines
Abstract Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resist...
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Nature Portfolio
2025-02-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-025-89423-0 |
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author | Jiandong Li Yanxin Hu Jiayao Zhang Weiguang Zhang Jianhua Yu Baochun Lu |
author_facet | Jiandong Li Yanxin Hu Jiayao Zhang Weiguang Zhang Jianhua Yu Baochun Lu |
author_sort | Jiandong Li |
collection | DOAJ |
description | Abstract Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resistant cell models and evaluated their resistance by assessing cell proliferation, cell cycle arrest, and DNA damage. GEM-resistant cells exhibited significant tolerance to GEM-induced growth inhibition, reduced cell cycle arrest, and decreased DNA damage compared to parental cells. We then explored potential resistance mechanisms and found that pathways and targets such as epithelial-mesenchymal transition, PI3K/Akt, p53R2, and IGF-1R did not show a significant correlation with ICC resistance. Interestingly, our findings suggested that reactive oxygen species might promote GEM resistance in ICC. In conclusion, we characterized a GEM-resistant ICC model, which can be employed to investigate alternative resistance mechanisms and explore new treatment approaches. |
format | Article |
id | doaj-art-0cbd0f244f0743139c99e903f5f2ec8d |
institution | Kabale University |
issn | 2045-2322 |
language | English |
publishDate | 2025-02-01 |
publisher | Nature Portfolio |
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series | Scientific Reports |
spelling | doaj-art-0cbd0f244f0743139c99e903f5f2ec8d2025-02-09T12:37:41ZengNature PortfolioScientific Reports2045-23222025-02-0115111310.1038/s41598-025-89423-0Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell linesJiandong Li0Yanxin Hu1Jiayao Zhang2Weiguang Zhang3Jianhua Yu4Baochun Lu5Department of Hepato-Biliary-Pancreatic Surgery, Shaoxing People’s HospitalShaoxing University Affiliated First HospitalZhejiang University School of MedicineDepartment of Molecular Medicine and Clinical Laboratory, Shaoxing Second HospitalDepartment of Hepato-Biliary-Pancreatic Surgery, Shaoxing People’s HospitalDepartment of Hepato-Biliary-Pancreatic Surgery, Shaoxing People’s HospitalAbstract Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver tumor associated with a dismal prognosis, largely due to chemotherapy resistance. However, the mechanisms underlying gemcitabine (GEM) resistance in ICC remain poorly understood. In this study, we established three GEM-resistant cell models and evaluated their resistance by assessing cell proliferation, cell cycle arrest, and DNA damage. GEM-resistant cells exhibited significant tolerance to GEM-induced growth inhibition, reduced cell cycle arrest, and decreased DNA damage compared to parental cells. We then explored potential resistance mechanisms and found that pathways and targets such as epithelial-mesenchymal transition, PI3K/Akt, p53R2, and IGF-1R did not show a significant correlation with ICC resistance. Interestingly, our findings suggested that reactive oxygen species might promote GEM resistance in ICC. In conclusion, we characterized a GEM-resistant ICC model, which can be employed to investigate alternative resistance mechanisms and explore new treatment approaches.https://doi.org/10.1038/s41598-025-89423-0 |
spellingShingle | Jiandong Li Yanxin Hu Jiayao Zhang Weiguang Zhang Jianhua Yu Baochun Lu Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines Scientific Reports |
title | Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines |
title_full | Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines |
title_fullStr | Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines |
title_full_unstemmed | Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines |
title_short | Establishment and characterization of three gemcitabine-resistant human intrahepatic cholangiocarcinoma cell lines |
title_sort | establishment and characterization of three gemcitabine resistant human intrahepatic cholangiocarcinoma cell lines |
url | https://doi.org/10.1038/s41598-025-89423-0 |
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